Module 9 2024

03/09/2024

FDA Guidance Aligns with ICH Q5E

• Demonstration of Comparability of Human Biological Products, Including Therapeutic Biotechnology-derived Products

– CBER/CDER, April 1996

– Aim is safe, pure, potent and effective demonstration

• Guidance for Industry: Comparability Protocols for Human Drugs and Biologicals - Chemistry, Manufacturing, and Controls Information

– CDER/CBER, Draft April 2016

– Provides framework for assessing a change within the company

– Allows changes falling within pre-agreed protocol (acceptance limits/tests etc) to have a reduced reporting (e.g. CBE not PA supplement)

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Comparability considerations

Task

Consideration

Risk assessment

Determine what may be impacted and prepare a risk based analysis plan

Must justify selection, it cannot be ‘cherry picked’ batches. In early development this may be a single batch (the pilot/tox batch), in late development this could consist data from all clinical/full scale batches Must justify selection, it cannot be ‘cherry picked’ batches. In early development this may be a single batch (the first post-change batch representing the new process) or later in development this may need to be at least 3 batches Otherwise, ensure appropriate reference standards are analysed on each occasion as a baseline control Based on capability of the method, process knowledge and understanding and stage of development. For example: qualitative parameters: comparable profiles, quantitative parameters mean of pre-change data ±3 SD and impurities: no new or higher level of impurities in the post change batches Aim for head-to-head testing where possible to reduce impact of variability

Define the pre-change batch(es) to compare

Define the post change batch(es) to compare

Define analytical testing strategy

Define acceptance criteria

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